Noroxin

Norfloxacin is used to treat certain types of infections, including infections of the urinary tract and prostate (a male reproductive gland). Norfloxacin is in a class of antibiotics called fluoroquinolones. It works by killing bacteria that cause infections. Antibiotics will not work for colds, flu, or other viral infections.

Norfloxacin is an antibiotic in a group of drugs called fluoroquinolones (flor-o-KWIN-o-lones). Norfloxacin fights bacteria in the body.

Norfloxacin is used to treat different bacterial infections of the prostate or urinary tract (bladder and kidneys). Norfloxacin is also used to treat gonorrhea.

Norfloxacin may also be used for purposes not listed in this medication guide.

You should not use this medication if you have ever had swelling or tearing of a tendon caused by taking norfloxacin or similar antibiotics.

You may not be able to use norfloxacin if you have a muscle disorder. Tell your doctor if you have a history of myasthenia gravis.

Norfloxacin may cause swelling or tearing of a tendon (the fiber that connects bones to muscles in the body), especially in the Achilles' tendon of the heel. This effect may be more likely to occur if you are over 60, if you take steroid medication, or if you have had a kidney, heart, or lung transplant.

Stop taking norfloxacin and call your doctor at once if you have sudden pain, swelling, bruising, tenderness, stiffness, or movement problems in any of your joints. Rest the joint until you receive medical care or instructions.

You should not use this medication if you are allergic to norfloxacin, or if:

• you have ever had swelling or tearing of a tendon caused by taking norfloxacin or similar antibiotics; or
• you are allergic to other fluoroquinolones (ciprofloxacin, gemifloxacin, levofloxacin, moxifloxacin, ofloxacin, and others).

You may not be able to use norfloxacin if you have a muscle disorder. Tell your doctor if you have a history of myasthenia gravis.

To make sure norfloxacin is safe for you, tell your doctor if you have:

• a heart rhythm disorder, especially if you take medication to treat it;
• slow heartbeats, or a personal or family history of Long QT syndrome;
• tendon problems, arthritis or other joint problems;
• a muscle or nerve disorder;
• kidney or liver disease;
• seizures or epilepsy;
• a history of head injury or brain tumor;
• a history of allergic reaction to an antibiotic;
• diabetes (especially if you take oral diabetes medication);
• low levels of potassium in your blood (hypokalemia); or
• if you use a blood thinner (warfarin, Coumadin) and have "INR" or prothrombin time tests.

Norfloxacin may cause swelling or tearing of a tendon (the fiber that connects bones to muscles in the body), especially in the Achilles' tendon of the heel. This can happen during treatment or up to several months after you stop taking norfloxacin. Tendon problems may be more likely to occur if you are over 60, if you take steroid medication, or if you have had a kidney, heart, or lung transplant.

FDA pregnancy category C. It is not known whether norfloxacin will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

It is not known whether norfloxacin passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

NOROXIN is indicated for the treatment of adults with the following infections caused by susceptible strains of the designated microorganisms:

Urinary Tract Infections

Uncomplicated urinary tract infections (including cystitis) due to Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Staphylococcus epidermidis, Staphylococcus saprophyticus, Citrobacter freundii1, Enterobacter aerogenes1, Enterobacter cloacae1, Proteus vulgaris1, Staphylococcus aureus1, or Streptococcus agalactiae1.

Because fluoroquinolones, including NOROXIN, have been associated with serious adverse reactions (see WARNINGS), and for some patients uncomplicated urinary tract infection is self-limiting, reserve NOROXIN for treatment of uncomplicated urinary tract infections (including cystitis) in patients who have no alternative treatment options.

Complicated urinary tract infections due to Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, or Serratia marcescens1. Sexually transmitted diseases (see WARNINGS)

Uncomplicated urethral and cervical gonorrhea due to Neisseria gonorrhoeae.

Prostatitis

Prostatitis due to Escherichia coli.

(See DOSAGE AND ADMINISTRATION for appropriate dosing instructions.)

Penicillinase production should have no effect on norfloxacin activity.

Appropriate culture and susceptibility tests should be performed before treatment in order to isolate and identify organisms causing the infection and to determine their susceptibility to norfloxacin. Therapy with norfloxacin may be initiated before results of these tests are known; once results become available, appropriate therapy should be given. Repeat culture and susceptibility testing performed periodically during therapy will provide information not only on the therapeutic effect of the antimicrobial agents but also on the possible emergence of bacterial resistance.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of NOROXIN and other antibacterial drugs, NOROXIN should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Noroxin falls into category C. In animal studies, pregnant animals were given this medication and had some babies born with problems. No well-controlled studies have been done in humans. Therefore, this medication may be used if the potential benefits to the mother outweigh the potential risks to the unborn child.

Tell your healthcare provider if you are breastfeeding or planning to breastfeed. It is not known if Noroxin passes into breast milk. You and your healthcare provider should decide whether you will take Noroxin or breastfeed.

• Take Noroxin exactly as prescribed by your healthcare provider.
• Noroxin is usually taken every 12 hours for patients with normal kidney function.
• Take Noroxin with a glass of water.
• Drink plenty of fluids while taking Noroxin .
• Take Noroxin at least one hour before or 2 hours after a meal or having milk or other dairy products.
• Do not skip any doses, or stop taking Noroxin even if you begin to feel better, until you finish your prescribed treatment, unless:
  • you have tendon effects,
  • you have a serious allergic reaction, or
  • your healthcare provider tells you to stop. This will help make sure that all of the bacteria are killed and lower the chance that the bacteria will become resistant to Noroxin. If this happens, Noroxin and other antibiotic medicines may not work in the future.
• If you miss a dose of Noroxin, take it as soon as you remember. Do not take two doses of Noroxin at the same time. Do not take more than 2 doses of Noroxin in one day.
• If you take too much, call your healthcare provider or get medical help immediately.

What to avoid while taking :

• Noroxin can make you feel dizzy and lightheaded. Do not drive, operate machinery, or do other activities that require mental alertness or coordination until you know how Noroxin affects you.
• Avoid sunlamps and tanning beds, and try to limit your time in the sun. Noroxin can make your skin sensitive to the sun (photosensitivity) and the light from sunlamps and tanning beds. You could get severe sunburn, blisters or swelling of your skin. If you get any of these symptoms while taking Noroxin, call your healthcare provider right away. You should use sunscreen and wear a hat and clothes that cover your skin if you have to be in sunlight.

• Store between 59-86°F (15-30°C).
• Keep container closed tightly.
• Keep Noroxin and all medicines out of the reach of children.

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

• It is used to treat bacterial infections.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache.
• Dizziness.
• Upset stomach or throwing up.
• Stomach cramps.
• Heartburn.
• Loose stools (diarrhea).

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

General

Needle-shaped crystals were found in the urine of some volunteers who received either placebo, 800 mg norfloxacin, or 1600 mg norfloxacin (at or twice the recommended daily dose, respectively) while participating in a double-blind, crossover study comparing single doses of norfloxacin with placebo. While crystalluria is not expected to occur under usual conditions with a dosage regimen of 400 mg b.i.d., as a precaution, the daily recommended dosage should not be exceeded and the patient should drink sufficient fluids to ensure a proper state of hydration and adequate urinary output.

Alteration in dosage regimen is necessary for patients with impaired renal function (see DOSAGE AND ADMINISTRATION).

Moderate to severe photosensitivity/phototoxicity reactions, the latter of which may manifest as exaggerated sunburn reactions (e.g., burning, erythema, exudation, vesicles, blistering, edema) involving areas exposed to light (typically the face, "V" area of the neck, extensor surfaces of the forearms, dorsa of the hands), can be associated with the use of quinolone antibiotics after sun or UV light exposure. Therefore, excessive exposure to these sources of light should be avoided. Drug therapy should be discontinued if phototoxicity occurs (see ADVERSE REACTIONS, Post-Marketing).

Rarely, hemolytic reactions have been reported in patients with latent or actual defects in glucose-6-phosphate dehydrogenase activity who take quinolone antibacterial agents, including norfloxacin (see ADVERSE REACTIONS).

Prescribing Noroxin in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Information for Patients

Patients should be advised:

 to contact their healthcare provider if they experience pain, swelling, or inflammation of a tendon, or weakness or inability to use one of their joints; rest and refrain from exercise; and discontinue Noroxin treatment. The risk of severe tendon disorders with fluoroquinolones is higher in older patients usually over 60 years of age, in patients taking corticosteroid drugs, and in patients with kidney, heart or lung transplants.

that fluoroquinolones like Noroxin may cause worsening of myasthenia gravis symptoms, including muscle weakness and breathing problems. Patients should call their healthcare provider right away if they have any worsening muscle weakness or breathing problems.

that norfloxacin may cause changes in the electrocardiogram (QTc interval prolongation).

that norfloxacin should be avoided in patients receiving class IA (e.g., quinidine, procainamide) or class III (e.g., amiodarone, sotalol) antiarrhythmic agents.

that norfloxacin should be used with caution in subjects receiving drugs that affect the QTc interval such as cisapride, erythromycin, antipsychotics, and tricyclic antidepressants.

to inform their physicians of any personal or family history of QTc prolongation or proarrhythmic conditions such as hypokalemia, bradycardia or recent myocardial ischemia.

that peripheral neuropathies have been associated with the use of norfloxacin that symptoms may occur soon after initiation of therapy and may be irreversible. If symptoms of peripheral neuropathy including pain, burning, tingling, numbness, and/or weakness develop, patients should immediately discontinue norfloxacin and contact their physicians.

to drink fluids liberally.

that norfloxacin should be taken at least one hour before or at least two hours after a meal or ingestion of milk and/or other dairy products.

that multivitamins or other products containing iron or zinc, antacids or Videx®3 (Didanosine), chewable/buffered tablets or the pediatric powder for oral solution, should not be taken within the two-hour period before or within the two-hour period after taking norfloxacin (see PRECAUTIONS, Drug Interactions).

that norfloxacin can cause dizziness and lightheadedness and, therefore, patients should know how they react to norfloxacin before they operate an automobile or machinery or engage in activities requiring mental alertness and coordination.

that norfloxacin may be associated with hypersensitivity reactions, even following the first dose, and to discontinue the drug at the first sign of a skin rash or other allergic reaction.

that photosensitivity/phototoxicity has been reported in patients receiving quinolones. Patients should minimize or avoid exposure to natural or artificial sunlight (tanning beds or UVA/B treatment) while taking quinolones. If patients need to be outdoors while using quinolones, they should wear loose-fitting clothes that protect skin from sun exposure and discuss other sun protection measures with their physician. If a sunburn-like reaction or skin eruption occurs, patients should contact their physician.

that some quinolones may increase the effects of theophylline and/or caffeine (see PRECAUTIONS, Drug Interactions).

that convulsions have been reported in patients taking quinolones, including norfloxacin, and to notify their physician before taking this drug if there is a history of this condition.

that diarrhea is a common problem caused by antibiotics, which usually ends when the antibiotic is discontinued. Sometimes after starting the treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

Patients should be counseled that antibacterial drugs including Noroxin should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Noroxin is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Noroxin or other antibacterial drugs in the future.

Registered trademark of Bristol-Myers Squibb Company

Laboratory Tests

As with any potent antibacterial agent, periodic assessment of organ system functions, including renal, hepatic, and hematopoietic, is advisable during prolonged therapy.

Drug Interactions

Quinolones, including norfloxacin, have been shown in vitro to inhibit CYP1A2. Concomitant use with drugs metabolized by CYP1A2 (e.g., caffeine, clozapine, ropinirole, tacrine, theophylline, tizanidine) may result in increased substrate drug concentrations when given in usual doses. Patients taking any of these drugs concomitantly with norfloxacin should be carefully monitored.

Elevated plasma levels of theophylline have been reported with concomitant quinolone use. There have been reports of theophylline-related side effects in patients on concomitant therapy with norfloxacin and theophylline. Therefore, monitoring of theophylline plasma levels should be considered and dosage of theophylline adjusted as required.

Elevated serum levels of cyclosporine have been reported with concomitant use of cyclosporine with norfloxacin. Therefore, cyclosporine serum levels should be monitored and appropriate cyclosporine dosage adjustments made when these drugs are used concomitantly.

Quinolones, including norfloxacin, may enhance the effects of oral anticoagulants, including warfarin or its derivatives or similar agents. When these products are administered concomitantly, prothrombin time or other suitable coagulation tests should be closely monitored.

The concomitant administration of quinolones including norfloxacin with glyburide (a sulfonylurea agent) has, on rare occasions, resulted in severe hypoglycemia. Therefore, monitoring of blood glucose is recommended when these agents are co-administered.

Diminished urinary excretion of norfloxacin has been reported during the concomitant administration of probenecid and norfloxacin.

The concomitant use of nitrofurantoin is not recommended since nitrofurantoin may antagonize the antibacterial effect of Noroxin in the urinary tract.

Multivitamins, or other products containing iron or zinc, antacids or sucralfate, should not be administered concomitantly with, or within 2 hours of, the administration of norfloxacin, because they may interfere with absorption resulting in lower serum and urine levels of norfloxacin.

Videx® (Didanosine) chewable/buffered tablets or the pediatric powder for oral solution should not be administered concomitantly with, or within 2 hours of, the administration of norfloxacin, because these products may interfere with absorption resulting in lower serum and urine levels of norfloxacin.

Some quinolones have also been shown to interfere with the metabolism of caffeine. This may lead to reduced clearance of caffeine and a prolongation of the plasma half-life that may lead to accumulation of caffeine in plasma when products containing caffeine are consumed while taking norfloxacin.

The concomitant administration of a non-steroidal anti-inflammatory drug (NSAID) with a quinolone, including norfloxacin, may increase the risk of CNS stimulation and convulsive seizures. Therefore, Noroxin should be used with caution in individuals receiving NSAIDS concomitantly.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No increase in neoplastic changes was observed with norfloxacin as compared to controls in a study in rats, lasting up to 96 weeks at doses 8-9 times2 the usual human dose (on a mg/kg basis).

Norfloxacin was tested for mutagenic activity in a number of in vivo and in vitro tests. Norfloxacin had no mutagenic effect in the dominant lethal test in mice and did not cause chromosomal aberrations in hamsters or rats at doses 30-60 times2 the usual human dose (on a mg/kg basis). Norfloxacin had no mutagenic activity in vitro in the Ames microbial mutagen test, Chinese hamster fibroblasts and V-79 mammalian cell assay. Although norfloxacin was weakly positive in the Rec-assay for DNA repair, all other mutagenic assays were negative including a more sensitive test (V-79).

Norfloxacin did not adversely affect the fertility of male and female mice at oral doses up to 30 times2 the usual human dose (on a mg/kg basis).

Pregnancy

Pregnancy Category C

Norfloxacin has been shown to produce embryonic loss in monkeys when given in doses 10 times2 the maximum daily total human dose (on a mg/kg basis). At this dose, peak plasma levels obtained in monkeys were approximately 2 times those obtained in humans. There has been no evidence of a teratogenic effect in any of the animal species tested (rat, rabbit, mouse, monkey) at 6-50 times2 the maximum daily human dose (on a mg/kg basis). There are, however, no adequate and well-controlled studies in pregnant women. Norfloxacin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

It is not known whether norfloxacin is excreted in human milk.

When a 200-mg dose of Noroxin was administered to nursing mothers, norfloxacin was not detected in human milk. However, because the dose studied was low, because other drugs in this class are secreted in human milk, and because of the potential for serious adverse reactions from norfloxacin in nursing infants, a decision should be made to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

The safety and effectiveness of oral norfloxacin in pediatric patients and adolescents below the age of 18 years have not been established. Norfloxacin causes arthropathy in juvenile animals of several animal species. (See WARNINGS and ANIMAL PHARMACOLOGY.)

Geriatric Use

Geriatric patients are at increased risk for developing severe tendon disorders including tendon rupture when being treated with a fluoroquinolone such as Noroxin. This risk is further increased in patients receiving concomitant corticosteroid therapy. Tendinitis or tendon rupture can involve the Achilles, hand, shoulder, or other tendon sites and can occur during or after completion of therapy; cases occurring up to several months after fluoroquinolone treatment have been reported. Caution should be used when prescribing Noroxin to elderly patients, especially those on corticosteroids. Patients should be informed of this potential side effect and advised to discontinue Noroxin and contact their healthcare provider if any symptoms of tendinitis or tendon rupture occur (see Boxed Warning; WARNINGS; and ADVERSE REACTIONS, Post-Marketing).

Of the 340 subjects in one large clinical study of Noroxin for treatment of urinary tract infections, 103 patients were 65 and older, 77 of whom were 70 and older; no overall differences in safety and effectiveness were evident between these subjects and younger subjects. In clinical practice, no difference in the type of reported adverse experiences have been observed between the elderly and younger patients except for a possible increased risk of tendon rupture in elderly patients receiving concomitant corticosteroids (see WARNINGS). In addition, increased risk for other adverse experiences in some older individuals cannot be ruled out (see ADVERSE REACTIONS).

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function (see DOSAGE AND ADMINISTRATION).

A pharmacokinetic study of Noroxin in elderly volunteers (65 to 75 years of age with normal renal function for their age) was carried out (see CLINICAL PHARMACOLOGY).

In general, elderly patients may be more susceptible to drug-associated effects of the QTc interval. Therefore, precaution should be taken when using Noroxin concomitantly with drugs that can result in prolongation of the QTc interval (e.g., class IA or class III antiarrhythmics) or in patients with risk factors for torsades de pointes (e.g., known QTc prolongation, uncorrected hypokalemia).

1. Clinical and Laboratory Standards Institute, Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically - Eighth edition, Approved Standard CLSI Document M7-A8, Vol. 29, No. 2, CLSI, Wayne, PA, 2009.
2. Clinical and Laboratory Standards Institute, Performance standards for antimicrobial disk susceptibility tests - Tenth edition, Approved Standard CLSI Document M2-A10, Vol. 29, No. 1, CLSI, Wayne, PA, 2009.

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MERCK & CO., INC., Whitehouse Station, NJ 08889, USA

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All rights reserved.

Revised: 08/2013

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